Email

Washington, DC—Children’s National Medical Center, Carolinas Medical Center, and AVI BioPharma will work together to develop a new treatment aimed at skipping exon 45, one of the most common exons affected in Duchenne muscular dystrophy (DMD).

The partnership will perform studies required for the new therapeutic, an exon-skipping drug candidate based on AVI’s phosphorodiamidate morpholino oligomers (PMO) chemistry, to become eligible for Investigational New Drug (IND) status. This status would allow for evaluation of the drug to begin in human clinical trials. The work is made possible by two grants, one from the Department of Defense’s Congressionally Directed Medical Research Program to Children’s National, and the other from a National Institute of Neurological Disorders and Stroke (NINDS) grant to Carolinas Medical Center in Charlotte, N.C.

“Exon skipping holds promise to significantly improve the quality of life for boys with Duchenne muscular dystrophy,” said Eric Hoffman, PhD, Center Director of Genetic Medicine Research at Children’s National. “We know, however, that to truly improve outcomes for this disease, we need to develop drugs to target the range of affected exons in DMD patients. This partnership adds a target for exon 45 to the investigational drugs targeting other exons that are in development around the world.”

This type of personalized drug development focuses on a series of small molecule drugs, called antisense oligonucleotides (AOs), which target specific mutations in the dystrophin gene to partially correct the DMD genetic defect at the mRNA splicing level. The approach, called “exon skipping,” is intended to help DMD patients produce dystrophin, the protein that is missing in their muscles. Exons are those segments on a gene that contain the necessary genetic information to produce a protein.

“We believe this work on exon 45 is an important component in the strategy to develop a portfolio of exon-skipping compounds for Duchenne muscular dystrophy,” said Qi Lu, MD, PhD, director of McColl Lockwood Laboratory at Carolinas Medical Center. “By working to bring the exon 45 therapeutic to IND status, we will be closer to reaching larger numbers of patients who are suffering from this devastating disease. Optimizing care for these children is imperative.”

“It is a great privilege to be working on a project of this magnitude,” said Susan Sparks, MD, a pediatrician at Levine Children’s Hospital in Charlotte who is collaborating with Qi Lu on exon-skipping research. “Every day, in my clinical settings, I see the impact of this disease on patients and their families. I am very excited to be testing new therapies that can potentially make a real difference for those affected by Duchenne.”

Chris Garabedian, president and CEO of AVI BioPharma, stated that, “Programs like this that join the medical expertise of pharmaceutical companies with academic medical centers, like Children’s National and Carolinas Medical Center, facilitate the advancement of therapeutics in DMD in new, more effective ways.”

This partnership is one of several collaborations underway to earn federal approval for exon-skipping therapeutics. Each DMD patient may have a different exon affected, and therefore need a slightly different formulation. AVI BioPharma, Children’s National Medical Center, and Carolinas Medical Center, along with several other national and international institutions, are working to bring treatments for several exon variations to the clinical setting as fast as possible in order to combat DMD for a majority of children with the disease.

“If we can show the efficacy and safety for two or three exon-specific drugs and these drugs behave similarly, we hope this will facilitate the regulatory pathway for subsequent exon skipping drugs based on the same chemistry,” said Edward Connor, MD, director of the Office of Innovation Development and Investigational Therapeutics and the Principal Investigator for the Department of Defense grant that is part of this collaboration. “The work with AVI BioPharma is designed to advance evaluation of the exon 45 drug in parallel with AVI’s programs for other exons, so that data about the safety and efficacy of this drug is available as soon as possible.”

About Duchenne Muscular DystrophyDuchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy and is one of the most common fatal genetic disorders affecting children worldwide. About one in every 3,500 males is born with DMD. Girls are rarely affected by the disorder. DMD is characterized by severe muscle wasting caused by various errors in the gene that codes for dystrophin, a protein that is an important structural component within muscle tissue. Symptoms usually appear before age 5. Progressive muscle weakness is typically first observed in the lower extremities and eventually spreads to the arms, neck and other areas. Most patients require use of a wheelchair by age 12 and the disease eventually causes complete paralysis and increasing difficulty in breathing requiring ventilator support and cardiac muscle function leading to heart failure. The disease is lethal, with death usually occurring before the age of 30. The outpatient cost of care for a non-ambulatory patient is very high. There are currently no cures or disease modifying therapies for DMD.

About the Carolinas HealthCare SystemCarolinas HealthCare System (www.carolinashealthcare.org), one of the nation's leading and most innovative healthcare organizations, provides a full spectrum of healthcare and wellness programs throughout North and South Carolina. Its diverse network of more than 650 care locations includes Carolinas Medical Center and Levine Children’s Hospital, as well as other academic medical centers, hospitals, healthcare pavilions, physician practices, destination centers, surgical and rehabilitation centers, home health agencies, nursing homes and hospice and palliative care. CHS works to improve and enhance the overall health and wellbeing of its communities through high quality patient care, education and research programs, and a variety of collaborative partnerships and initiatives.

About Children’s National Health System

Children’s National Health System, based in Washington, DC, has been serving the nation’s children since 1870. Children’s National is Magnet® designated, and was ranked among the top 10 pediatric hospitals by U.S. News & World Report 2015-16. Home to the Children’s Research Institute and the Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National is one of the nation’s top NIH-funded pediatric institutions. With a community-based pediatric network, seven regional outpatient centers, an ambulatory surgery center, two emergency rooms, an acute care hospital, and collaborations throughout the region, Children’s National is recognized for its expertise and innovation in pediatric care and as an advocate for all children. For more information, visit ChildrensNational.org, or follow us on Facebook and Twitter.